Vesicles, Pustules, Bullae, Erosions, and Ulcerations
Renee M. Howard, Ilona J. Frieden
Introduction
Vesiculopustular and bullous disorders are common in the neonatal period and the first years of life. Accurate and prompt diagnosis is essential because some conditions that present with blisters and pustules are truly life-threatening. In contrast, many others are innocuous and self-limited; misdiagnosis of a more serious condition can lead to iatrogenic complications, unnecessary expense, and parental anguish.
The causes of blisters and pustules in newborns and young infants are influenced by the clinical setting, including geography and whether patients are seen in a hospital or clinic. Infection is the most common etiology in developing countries. In a study of neonates in India with blisters and pustules, bacterial infection was the most common overall, whereas erythema toxicum was the most prevalent non-infectious etiology.1 In a prospective study of newborn inpatients in California examined by pediatric dermatologists, the most common eruption in newborns was erythema toxicum.2 In a retrospective European study done in a Level 3 nursery, vesicles and pustules were the sole reason for admission to the Neonatal Intensive Care Unit (NICU) in 29.8% of infants admitted because of skin lesions.3
Several articles have reviewed an approach to infants with these cutaneous findings,4–6 including infants with hemorrhagic vesiculopustules.7 There is also considerable overlap with the subject matter in other chapters of this book, most notably Chapter 7 (Transient Benign Cutaneous Lesions in the Newborn), and Chapters 12, 13 and 14 (Bacterial, Viral, and Fungal Infections, respectively), so the main discussion of specific disorders are discussed therein. Chapter 11 discusses the diagnosis and management of epidermolysis bullosa and other non-infectious causes of bullae, so those conditions are covered in far less detail in this chapter.
In addition to a discussion of vesicles, pustules and bullae, this chapter also includes conditions presenting with erosions and ulcerations. Although vesicles, pustules, and bullae are primary skin lesions, they can quickly progress to secondary skin lesions (i.e. erosions and ulcerations). This can occur rapidly or have transpired in utero, such that erosions and ulcerations are the main presenting finding. Examples include staphylococcal scalded skin syndrome, where erythema and skin erosions predominate over blisters, and Pseudomonas skin infection, where pustules rapidly evolve into necrotic ulcers.
Because of the wide range of diagnoses discussed in this chapter, there are boxes and tables to help with a systematic approach to evaluation and differential diagnosis. Tables 10.1–10.3 summarize key findings and differential diagnosis of vesiculopustular diseases in newborns and infants, including infectious causes, relatively common transient skin lesions, and uncommon and rare causes of this clinical presentation. Tables 10.4–10.6 summarize these same categories for the differential diagnosis of bullae, erosions, and ulcerations. Box 10.1 lists conditions in neonates where pustules and vesicles predominate, Box 10.2 lists the conditions in neonates where bullae predominate, and Box 10.3 lists conditions in neonates where erosions or ulcerations may predominate.
TABLE 10.1
Differential diagnosis of vesiculopustular diseases in newborns and infants – Infectious causes
| Disease | Usual age of onset | Skin: morphology | Skin: usual distribution | Clinical: other | Diagnosis/findings |
| Staphylococcal pyoderma | Neonatal through infancy | Pustules, bullae, occasionally vesicles; crusted impetigo, folliculitis with follicular-based papules, pustules or furuncles | Any site: in neonates often concentrated in the diaper area and periumbilical skin. Infants: anywhere but often in fold areas, around mouth and nose. Perianal erythema similar to perianal Strep. |
If toxin-producing S. aureus may occur in epidemics. In this setting, often collarettes of scale at periphery | Gram stain: PMNs Gram-positive cocci in clusters. Bacterial culture |
| Group A streptococcal infection | Neonatal through infancy | Isolated pustules, honey-crusted areas, bullae, moist erythema. Perianal erythema with or without fissures, erosions or pustules. Blistering distal dactylitis |
Any site including palms, soles. In older infants characteristic presentations may include blistering distal dactylitis on volar fingertips; perianal ‘dermatitis’ |
Rare in neonates but may have other findings suggesting sepsis. Infants may have fever or other signs of systemic infection (more than with S. aureus), positive history of exposure to Strep. throat in family member |
Gram stain: Gram-positive cocci in chains; bacterial culture, rapid Strep. test. In older children throat culture may also be positive |
| Group B streptococcal infection (GBS) | In neonates – rare. In infants uncommon but similar to Group A Strep. infection |
Vesicles bullae, erosions, honey-crusted lesions | Any area including perianal and distal dactylitis | Neonates may have GBS systemic infection. In older children GBS is not always a pathogen – can represent colonization | Gram stain: Gram-positive cocci in chains; bacterial culture |
| Listeriosis | Birth, first few hours | Hemorrhagic pustules and petechiae | Generalized, especially trunk and extremities | Sepsis; respiratory distress; maternal fever, preterm labor | Gram-positive rods; bacterial culture skin and other sites |
| Haemophilus influenzae infection | Birth or first few days | Vesicles, crusted areas | No specific site predisposed | Bacteremia, meningitis may be present | Gram-negative bacilli; bacterial culture |
| Pseudomonas infection | Days to weeks. Later onset months to years |
Erythema, pustules, hemorrhagic bullae, necrotic ulcerations | Any area, but especially diaper, periorificial | History of illness in neonatal period, Immunocompromised host; occasionally immunocompetent infant | Skin or tissue Gram stain: Gram-negative rods; cultures skin, blood |
| Congenital and neonatal candidiasis | Birth or first few days of life | Erythema, small papules and pustules. Burn-like dermatitis with scaling may develop in extremely premature infants even after a few weeks of life |
Any part of body; upper torso, palms, soles often involved | Risk factors include prematurity. Foreign body in cervix/uterus |
KOH: hyphae, budding yeast; placental lesions. Skin culture can grow on standard bacterial media. Skin biopsy may be helpful if KOH negative |
| Candida albicans infection | Neonates and infants | Usual: Beefy red patches with overlying fine scale, satellite papules and pustules. Less common: moist erythema in folds |
Diaper or other intertriginous area | Usually otherwise healthy | KOH: hyphae, budding yeast if pustules are present |
| Aspergillus infection | Few days to weeks | Pustules often clustered, rapidly evolve to ulcers | Any area | Extreme prematurity usually present | Skin biopsy: septate hyphae; tissue fungal culture |
| Intrauterine herpes simplex | Birth; first few days of life | Vesicles, pustules, widespread erosions, congenital scars, areas of missing skin | Any site but scalp often affected with aplasia cutis-like areas | Signs of TORCH infections, e.g., low-birthweight; microcephaly, chorioretinitis | Tzanck; FA or immunoperoxidase slide test, PCR, viral culture |
| Neonatal herpes simplex | Usually 5–14 days | Vesicles, pustules, crusts, erosions | Any site; especially scalp, torso; may involve mucosa | Signs of sepsis; irritability, lethargy | Tzanck; FA or immunoperoxidase slide test, PCR, viral culture |
| Herpes simplex infection: older infants | Weeks to years | Primary gingivostomatitis. Recurrent HSV Eczema herpeticum: erosions, small vesicles and punched-out erosions Herpetic whitlow: grouped vesicles, pustules or bullae |
Intra- and perioral vesicles erosions and erythema Grouped vesicles erythematous base, any site Often face but any site – pattern may be grouped in some areas but trail off in others Acral skin, usually finger or toe |
Fever, irritability, adenopathy if primary. Often recurs in same site, sun exposure may provoke. In setting of atopic dermatitis, usual moderate to severe. May mimic bacterial dactylitis |
Tzanck; FA or immunoperoxidase slide test, PCR, viral culture |
| Neonatal varicella | 0–14 days | Vesicles on erythematous base; Lesions usually in same stage of development | Generalized distribution, often much more widespread than outside newborn period | Maternal primary varicella infection 7 days before to 2 days after delivery | Tzanck, FA, viral culture |
| Herpes zoster | Neonates and infants | Vesicles on erythematous base in dermatomal pattern | Typically extremity or torso | Maternal primary varicella infection during pregnancy OR primary varicella early in life | Tzanck, FA, viral culture |
| Primary varicella (Chickenpox) | Weeks to years | Crops of lesions at varying stages. Vesicles on erythematous base | Often starts on scalp, with accentuation of torso, but can be generalized | More common in unimmunized infants but can occur in less pronounced form in immunized infants (usually less vesicular) | Tzanck, FA, viral culture |
| Enteroviral exanthems | Weeks to years | Hand, foot, mouth: oval gray vesicles; Other enteroviral exanthems; Small vesicles, bullae, eczema herpeticum-like petechial |
Intraoral; Acral distribution with accentuation of palms, soles, diaper area Generalized |
Occasionally fever, vomiting, diarrhea, upper respiratory symptoms; Skin pain or itch; Several weeks later: onychomadesis |
PCR or viral culture: best yield are nasopharynx, rectum, vesicular skin lesions |
| Scabies | Usually 3–4 weeks or older | Multiple morphologies in the same patient i.e., papules, wheals, nodules, crusted areas, vesicles, burrows | Accentuated axillae, feet, wrists, may occur anywhere | Pruritus. Usually family members with itching, rash | Scabies prep demonstrating mites, eggs, or feces; clinical |
| Chikungunya virus | Infants, weeks to years | Vesicles or bullae | Generalized | Epidemics in developing countries; Fever |
TABLE 10.2
Differential diagnosis of vesiculopustular diseases – Transient skin lesions
| Disease | Usual age of onset | Skin: morphology | Skin: usual distribution | Clinical: other | Diagnosis/findings |
| Erythema toxicum neonatorm | Usually 24–28 h, but can be birth to 2 weeks | Erythematous macules, papules, pustules, wheals | Anywhere except palms, soles | Term infants >2500 g | Clinical; Wright’s stain: eosinophils |
| Neonatal pustular melanosis | Birth or shortly thereafter but collarettes of scale or hyperpigmented macules occasionally noted at a few days to weeks; not at birth | Pustules without underlying erythema; collarettes of scale; hyperpigmented macules; lesions may be clustered together | Anywhere; most often forehead, ears, back, fingers, toes | Term infants; more common in black infants | Clinical; Wright’s stain: PMNs, occasional eosinophil, cellular debris |
| Miliaria crystallina | Birth, neonatal period or later in infancy | Fragile vesicles without underlying erythema | Forehead, upper trunk, arms most common | Can be congenital but in acquired cases typically a history of fever | Clinical; Wright, Gram and Tzanck preps negative |
| Miliaria rubra | Neonatal or infancy | Erythematous papules with superimposed pustules typically concentrated in one or two areas; not generalized | Forehead, upper trunk, arms most common | Sometimes history of overwarming, fever, or use of occlusive dressing or garment | Clinical; Wright, Gram and Tzanck preps negative |
| Neonatal ‘acne’ (benign cephalic pustulosis) | Days to weeks | Papules and pustules on erythematous base | Cheeks, forehead, eyelids, neck, upper chest, scalp | Otherwise well; may have scaling in scalp | Usually clinical; Giemsa: negative or fungal spores, neutrophils |
TABLE 10.3
Differential diagnosis of vesiculopustular diseases – Uncommon and rare causes
| Disease | Usual age of onset | Skin: morphology | Skin: usual distribution | Clinical: other | Diagnosis/findings |
| Acropustulosis of infancy | Birth or days to weeks | Vesicles and pustules | Hands and feet, occasional lesion elsewhere | Severe pruritus accompanying lesions which tend to come in crops | Clinical; skin biopsy: intraepidermal vesicle/pustule |
| Eosinophilic pustular folliculitis | Birth or days to weeks | Pustules, erythema | Mainly scalp and face; occasionally trunk, extremities | Pruritus; waxing and waning course with recurrent crops | Skin biopsy: dense perifollicular mixed infiltrate with eosinophils |
| Incontinentia pigmenti | Birth to days | Vesicles, hyperkeratosis in linear array | Most common on trunk, scalp, extremities | Extracutaneous involvement common but often not evident at birth. Mothers may have history of IP or other findings (e.g., missing teeth, areas of decreased hair growth) |
Skin biopsy: eosinophilic spongiosis with dyskeratosis Gene testing can also be used to establish diagnosis in atypical cases |
| Neonatal Behçet disease | First week of life | Small punched out vesicles, pustules, ulcerations and scarring | Perioral and oral mucous membranes, hands and feet, occasionally other sites | Maternal history of Behçet disease | Clinical findings and maternal history |
| Erosive pustular dermatosis of the scalp | Weeks to months | Crusting, pustules, scaly erythema | Scalp, superimposed on areas of alopecia, scarring from scalp injury | Severe scalp edema or necrosis of delivery; similar findings in Hay–Wells and Rapp–Hodgkin ectodermal dysplasias | Clinical findings and prior history of scalp injury or ectodermal dysplasia |
| Hyper-IgE syndrome | Days to months | Single or grouped pustules, vesicles, or crusting | Face, scalp, upper torso | Blood eosinophilia Note: IgE levels often become elevated after neonatal period |
Skin biopsy: intraepidermal vesicle with eosinophils or eosinophilic folliculitis. Gene testing for STAT-3 mutation |
| Lipoid proteinosis | Usually ≥1 year | Erythematous papulovesicular lesions resulting in atrophic scarring | Face, ears, extremities and occasionally trunk | Thickening of the skin, especially lips, perinasal skin, tongue; hoarseness | Skin biopsy shows thick hyalinized material with characteristic PAS-positive staining. Positive FH in some cases |
| Pustular psoriasis or deficiency of interleukin-1 receptor antagonist | First weeks or months of life | Pustules generalized, but especially palms, soles; may have underlying erythroderma | Generalized | Irritability, occasionally fever | Skin biopsy: epidermal microabscesses and acanthosis, parakeratosis, dilated capillaries |
| Pustular eruption of myelodysplasia in Down syndrome/neonatal eosinophilic pustulosis | First few days to months of life | Extensive pustules on erythematous base, often aggregating in areas of skin injury | Face most common site but can occur elsewhere | Very high WBC count: usually in setting of Down syndrome but can occur without obvious Down phenotype or with other causes of severe leukocytosis |
